Procurement of Leukapheresis Products From End Stage Liver Disease (ESLD) Patients for Immunological Studies

End Stage Liver Disease Clinical Trial

Official title:

Procurement of Leukapheresis Products From End Stage Liver Disease (ESLD) Patients for Immunological Studies

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02447926
• Other study ID #: STU00097231
• Status: Terminated
• Phase: N/A
• Start date: July 2014
• Est. completion date: July 2016

Study information

• Verified date: August 2019
• Source: Northwestern University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Regulatory CD4+CD25+ T cells (Treg) derived from the thymus and/or periphery can control immune responsiveness to auto- and allo-antigens. However, there have been few efforts to harness the therapeutic potential of isolated Tregs to control graft rejection and inducing transplantation tolerance in solid organ recipients. In order for Tregs to be used as a clinical treatment, the following properties are necessary: ex vivo generation of sufficient numbers of cells, migration in vivo to sites of antigenic reactivity, ability to suppress rejection in an alloantigen-specific manner, and survival/expansion after infusion. The and others have demonstrated 1) the feasibility of expanding Treg ex vivo, 2) the ability of these cells to down-regulate allogeneic immune responses in vitro, and 3) the efficacy of Treg for prevention of allograft rejection in animal models. In kidney transplant, the investigators have developed strategies for the ex vivo expansion of naturally occurring human Tregs (nTregs) from leukapheresis products that would allow for the clinical employment of this cellular therapy. The investigators are also interested in this approach in patients with end stage liver disease (ESLD) undergoing liver transplantation (LT). Our central hypothesis is that alloreactive human nTreg with suppressive action can be expanded ex vivo from ESLD patients (this proposal) and used to both prevent liver transplant rejection and facilitate the minimization and withdrawal of drug-based immunosuppression (future proposals). This application will further define and validate efficient methods for ex vivo expansion of human CD4+CD25+CD127- FOXP3+nTregs cells in ESLD. The investigators herein propose to use leukapheresis products obtained from patients with ESLD to further refine and optimize protocols for expansion of Tregs. Suppressive function of expanded cells will be assessed using in vitro assays of alloreactivity (mixed lymphocyte culture).

Description:

Regulatory CD4+CD25+ T cells (Treg) derived from the thymus and/or periphery can control immune responsiveness to auto- and allo-antigens. However, there have been few efforts to harness the therapeutic potential of isolated Tregs to control graft rejection and inducing transplantation tolerance in solid organ recipients. In order for Tregs to be used as a clinical treatment, the following properties are necessary: ex vivo generation of sufficient numbers of cells, migration in vivo to sites of antigenic reactivity, ability to suppress rejection in an alloantigen-specific manner, and survival/expansion after infusion. We and others have demonstrated 1) the feasibility of expanding Treg ex vivo, 2) the ability of these cells to down-regulate allogeneic immune responses in vitro, and 3) the efficacy of Treg for prevention of allograft rejection in animal models. In kidney transplant, we have developed strategies for the ex vivo expansion of naturally occurring human Tregs (nTregs) from leukapheresis products that would allow for the clinical employment of this cellular therapy. We are also interested in this approach in patients with end stage liver disease (ESLD) undergoing liver transplantation (LT). Our central hypothesis is that alloreactive human nTreg with suppressive action can be expanded ex vivo from ESLD patients (this proposal) and used to both prevent liver transplant rejection and facilitate the minimization and withdrawal of drug-based immunosuppression (future proposals). This application will further define and validate efficient methods for ex vivo expansion of human CD4+CD25+CD127- FOXP3+nTregs cells in ESLD. We herein propose to use leukapheresis products obtained from patients with ESLD to further refine and optimize protocols for expansion of Tregs. Suppressive function of expanded cells will be assessed using in vitro assays of alloreactivity (mixed lymphocyte culture).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1
• Est. completion date: July 2016
• Est. primary completion date: July 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 89 Years

Eligibility

Inclusion Criteria:

• >18 years old,

• ESLD MELD <25,

• No recent infection,

• no hepatic decompensation,

• no history of HIV,

• weight > 110 lbs,

• platelets > 50,000,

• HGB >10,

• no prior organ transplant

Exclusion Criteria:

• Patients ineligible for liver transplant,

• patients who do not understand why the study procedures are being conducted,

• subjects who do not meet all inclusion criteria.

Related Conditions & MeSH terms

• End Stage Liver Disease
• Liver Diseases

Intervention

Procedure:
• Leukapheresis
Catheter placement will occur for about 1 hour. The research nurse will schedule leukapheresis on the next day following catheter placement. On the day of leukapheresis, a blood draw will monitor blood counts, kidney function, liver function, and blood clotting ability. Vital signs will be checked three times over the course of intervention. During the procedure, blood is mixed with anticoagulant and separated (i.e. red blood cells, white blood cells, platelets, and plasma). 1-1.5 cups of white blood cells will be collected. Leukapheresis will last 3-6 hours. Remaining components, except for 100-200 ml of plasma, are returned through the catheter. Two teaspoons of blood will be drawn to determine when catheter removal can occur. This part of intervention lasts about 2.5-4 hours.

Locations

Country	Name	City	State
United States	Northwestern University Comprehensive Transplant Center	Chicago	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
Northwestern University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Regulatory CD4+CD25+ T Cells Obtained From 150 ml of Peripheral Blood in an ESLD Patient	Number of regulatory CD4+CD25+ T cells after 21 days in culture from leukapheresis product (150 ml of processed blood) from ESLD patient.	21 days
Primary	Suppressive Function of Expanded Cells Will be Assessed Using in Vitro Assays of Alloreactivity (Mixed Lymphocyte Culture)	Assay testing - Suppressive function of expanded cells will be assessed using in vitro assays of alloreactivity (mixed lymphocyte culture). The in vitro assays will test whether the expanded Tregs will retain their suppressive function.	21 days